An immediate hypersensitivity response of the immune system can occur through the interaction of immunoglobulin E (IgE) and the receptor for IgE (FcE) present on the surface of mast cells and basophils in the presence of antigen which is capable of reacting with the FcE bound IgE.
The mast cell FcE receptors have a high affinity for the Fc region of the IgE molecule. Thus, when IgE becomes bound to the FcE receptor the specific antigen binding domains of the IgE molecule face outward from the mast cell to enable antigen specific binding to occur.
A key event in the initiation of allergic reactions is the high affinity binding of IgE to FcE receptors on mast cells or basophils (Ishizaka, et al., Journal of Immunology, 99: 1187, 1967). Subsequent cross-linking of mast cell bound IgE bound to adjacent FcE receptors activates the mast cell and results in degranulation. In so doing, the mast cells release a variety of the mediators such as histamine, serotonin and slow-reacting substance which cause many of the symptoms associated with allergies.
Cross-linking of the mast cell IgE receptor (FcE) and the resultant triggering of the mast cell can occur indirectly, when IgE is bound to nearby FcE receptors, or directly, using antibody specific for the FcE receptors themselves. Indirect cross-linking can occur when specific antigen is bound by IgE molecules on the cell surface, or by using anti-idiotype antibody, lectins, or anti-IgE molecule antibodies reactive with epitopes which are accessible even when the IgE is bound by the FcE receptor.
In addition to the high affinity FcE receptors on mast cells and basophils, receptors with low affinity for IgE have been detected on a number of other cell types including B and T lymphocytes, monocytes, eosinophils and platelets (Lawrence, et al., Journal of Clinical Investigation, 55: 268, l975). There is little or no structural similarity between the high and low affinity FcE receptors. Recently, the alpha chain of the high affinity mast cell receptor (Kinet, et al., Federation Proceedings (Abstract 6006), 46: 1346, 1987) and the low affinity receptor from B lymphocytes (Kikutani, et al., Cell, 47: 657, 1986) have been cloned. No sequence homology was detectable between the two receptors. Furthermore, there is evidence that even low affinity receptors expressed on different hematopoietic cells are heterogeneous since a monoclonal antibody to the murine B lymphocyte FcE receptor failed to react with mouse T cells or macrophages (Rao, et al. Journal of Immunology, 138: 1845, 1987).
The function of FcE receptors on different cell lineages is likely to be different. While FcE receptors on eosinophils and macrophages are probably involved in antibody-dependent cytotoxicity, receptors for IgE on lymphocytes are probably involved in immune regulation (Metzger, et al., Annual Reviews of Immunology, 4: 419, 1986).